| PART Ⅰ Time point independent tumor positivity of 68Ga-PSMA PET/CT Pre and Post-biopsy in high-risk prostate cancerObjective:Prostate-specific membrane antigen（PSMA）PET/CT imaging has gained increasing clinical importance for the detection and staging of high-risk primary prostate cancer（PCa）.However,it is unclear whether the routine practice of prostate biopsy obscures the image finding of PSMA PET/CT.This study aimed to compare the tumor positivity rate of PSMA PET/CT performed pre（PSMA PET/CTpre）and post biopsy(PSMA PET/CTpost)in high-risk PCa patients.Methods:We matched 58 PSMA PET/CTpost with 58 PSMA PET/CTpre studies for primary detection of high-risk PCa according to clinical characteristics.Three subgroups of PSMA PET/CTpost were defined by the intervals after biopsy（≤1 week,12 weeks,and 25 weeks）.Tumor positivity rates were determined and SUVmax of primary tumors were compared separately for the two main groups and the related subgroups.Malignant prostate tissues from 20 of these patients were examined by immunohistochemical analysis of PSMA.Additionally,the value of PSMA PET/CTpre and PSMA PET/CTpost in assessing seminal vesicle invasion（SVI）were evaluated in patients who underwent radical prostatectomy.Results:All the primary tumors were positive on PSMA PET/CTpost and PSMA PET/CTpre imaging,resulting in a patient-based positivity rates of 100%（58/58）in both groups.All examined IHC results（20/20）confirmed the high-level expression of PSMA.SUVmax of primary tumors did not differ between the two main groups（16.1,IQR 9.8-26.6 vs.16.5,IQR 11.0-26.7,P > 0.05）.Subgroup analysis of PSMA PET/CTpost（≤1 week,12 weeks,and 25 weeks）also showed no significant difference in tumor SUVmax（15.8,IQR 9.5-22.2;17.8,IQR 9.8-29.2;and 15.4,IQR 10.1-30.3.P > 0.05）.The primary tumor SUVmax was significantly higher in patients with locally advanced PC（≥ p T3;16.3,IQR 11.4-30.0）as compared with that in locally localized tumor（p T2;9.5,IQR 7.9-16.8）（P < 0.05）.Differences in primary tumor uptake were also recorded in individuals with or without metastases: N+ BM+（42.3%,49/116,median 16.6）,N-BM+（11.2%,13/116,11.5）,N+ BM-（17.2%,20/116,24.4）and N-BM-（29.3%,34/116,15.9）,respectively,P < 0.05).PSMA PET/CTpost and PSMA PET/CTpre exhibited similar value in SVI detection as well.A slight positive correlation was found between tumor SUVmax and the p T stage（r=0.316,P < 0.05）in patients who underwent radical prostatectomy as well as the tumor SUVmax and t PSA value（r = 0.358,P < 0.01）in PSMA PET/CTpre patients.However,no significant correlation between tumor SUVmax and pre-scan t PSA value was found in the PSMA PET/CTpost patients（r =-0.012,P > 0.05）.Also,ISUP grade was not correlated with the tumor SUVmax（r = 0.085,P > 0.05）.Conclusions:The tumor positivity rate was consistently high for PSMA PET/CTpre and Post-Biopsy.A prior biopsy does not seem to affect the tumor positivity rate of PSMA PET/CT in high-risk PCa.PART Ⅱ Utility of 68Ga-PSMA-617 PET/CT SUVmax value in distinguishing benign and malignant lesions of the prostateObjective:To evaluate SUVmax values in 68Ga-PSMA-617 PET/CT for differentiation of benign prostatic lesions from prostate cancer.Methods:A total of 46 men with suspected prostate cancer who underwent 68Ga-PSMA-617 PET/CT in our department were enrolled.SUVmax was measured for the hottest PSMA-avid prostate lesion.Pathological results from biopsy or radical prostatectomy were used for reference-standard.SUVmax,t PSA and mean age were compared for the two groups.Areas under receiver operating（ROC）characteristic curves were calculated for discriminating malignant vs.benign prostate lesions and optimal SUVmax-cutoff values were calculated using the Youden’s index for 68Ga-PSMA-617 and serum t PSA.Results:Thirty patients with malignant（65.22%）and 16 benign prostatic lesions（34.78%） were included.Median SUVmax in the malignant tumors were significantly higher than in the benign prostatic lesions detected by PSMA-617 PET/CT（11.45,IQR 7.75-18.35 vs.4.15,IQR 3.47-5.00,P < 0.001）.Patients with malignant tumors also exhibited higher t PSA level（19.41 ng/ml,IQR12.44-40.53 vs.10.82 IQR 6.08-25.82,P < 0.05）.By ROC analysis,the areas under the curve of PSMA-617 PET/CT SUVmax and serum t PSA in the diagnosis of prostate cancer were 0.963（P < 0.001）and 0.731（P < 0.05）,respectively.The recommended cutoff value of SUVmax for discriminating benign lesion from malignant prostatic lesion was set at 5.85 with a sensitivity of 90.0% and a specificity of 100%,respectively,the Youden’s index was 0.90.As for serum t PSA level,the optimal cutoff value was 11.19 ng/ml with a sensitivity of 86.7% and a specificity of 56.2%,respectively,however,the Youden’s index was only 0.42.Furthermore,the area under the curve of SUVmax + t PSA in the diagnosis of localized prostate cancer was 0.962（P < 0.001）.Conclusions:This pilot study shows that SUVmax values may serve as a predictive biomarker to identify malignant lesions in patients with suspected prostate cancer.PART Ⅲ Comparison of 68Ga-PSMA PET/CT,MRI and combination in the detection and pre-operative staging of clinically significant prostate cancerObjective:To compare the performance of 68Ga-prostate-specific membrane antigen（PSMA）PET/CT,MRI and PSMA PET/CT + mp MRI in preoperative primary detection and staging of clinically significant prostate cancer.Methods:Forty-two patients with clinically significant prostate cancer,who underwent preoperative 68Ga-PSMA PET/CT and prostate MRI in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology between April 2018 and April 2021 were retrospectively enrolled.The pathological and follow-up results were used as the gold-standard.The diagnostic performance of PSMA PET/CT,mp MRI and PSMA PET/CT + mp MRI for primary tumor,extracapsular extension,seminal vesicle and bladder invasion were compared,as well as nodal and bone metastases.The Chi-square test and Fisher’s exact test was used for data analysis.The value of PSMA PET/CT and mp MRI for T-staging evaluation were also determined.For comparisons of the tumor SUVmax between groups,p values were calculated by the Mann-Whitney U test.The correlations of tumor SUVmax with the t PSA level,PI-RADS score and ISUP grade were analyzed using Spearman’s correlation.Results:Prostate cancer was confirmed by surgery pathology in the 42 patients.The detection rate of 68Ga-PSMA PET/CT,MRI and PSMA PET/CT + mp MRI for primary prostate cancer 97.62%（41/42）,97.62%（41/42）and 100%（42/42）.PSMA PET/CT had higher specificity for detecting seminal vesicle invasion and extracapsular extension,however,MRI exhibited higher sensitivity（P < 0.05）.PSMA PET/CT had higher sensitivity and accuracy for detecting bladder invasion（P < 0.05）.PSMA PET/CT + mp MRI further improved the diagnostic performance.The sensitivity,specificity and accuracy of PSMA PET/CT for detecting pelvic lymph node metastasis were all 100%,and those of MRI for evaluating pelvic lymph node metastasis were 68.23%,93.10% and 85.71%,respectively.All the 8 patients with pelvic bone metastases were positive on PSMA PET/CT,but only 5 of them were positive on MRI.PSMA PET/CT outperformed MRI in evaluating nodal and bone metastases.The primary tumor SUVmax was significantly higher in high-risk patients as compared with that in intermediate risk patients（19.25 ± 2.21 vs.12.78 ± 1.14,P < 0.05）.A slight positive correlation was found between tumor SUVmax and the ISUP grade as well as the tumor SUVmax and t PSA value（r = 0.406、0.399,P < 0.05）.However,no significant correlation between PI-RADS score and t PSA value,nor ISUP grade was found（r = 0.287、-0.043,P > 0.05）Conclusions:68Ga-PSMA PET/CT and MRI have similar high accuracy in the detection and local staging of primary prostate cancer.PSMA PET/CT outperformed MRI in evaluating nodal and bone metastases.The combination of PSMA + MRI could further improve the diagnostic performance for detection and staging of clinically significant prostate cancer.PART Ⅳ Preliminary results on response assessment using 68Ga-PSMA PET/CT in patients undergoing systemic therapy for metastatic hormone-sensitive prostate cancerObjective:To investigate the usefulness of the positron emission tomography response criteria in solid tumors（PERCIST）and SUVmax values for predicting tumor response to systemic therapy in patients with metastatic hormone-sensitive prostate cancer（mHSPC）.Methods:We included mHSPC patients with either a post-treatment PSMA PET/CT scan or baseline + follow-up PSMA PET/CT performed at our institution.Two groups including PSMA-PET/CT-PERCIST-biochemical response（BR）groups and PSMA PET/CThistopathology group were defined.PSA response served as standard of reference in the PSMA-PET/CT-PERCIST-BR group.Mc Nemar’s test was used to compare the concordances between PERCIST responses assessed by PSMA PET/CT and biochemical responses assessed by PSA.Histopathology results from post-treatment radical prostatectomy were used for reference-standard in the PSMA PET/CT-histopathology group.Three types of pathological response were defined（0-1 pathological complete response,2 partial pathological response vs.3 nonpathological response）.SUVmax values and pathologic response were compared and correlated for the three types by Mann-Whitney u test and Spearman analysis.Results:A total of 14 and 17 patients were included in the PSMA-PET/CT-PERCISTbiochemical response（BR）and PSMA PET/CT-histopathology groups.14 patients in the PSMA PET/CT PERCIST-biochemical response（BR）group were all considered biochemical responders.There were 12 PSMA-PET/CT-PERCIST responders and 2 PSMAPET/CT-PERCIST nonresponders.The concordance rate between the PSMA-PET/CTPERCIST status of the primary tumor and the biochemical response was 85.71%（12/14）.No statistically significant difference was found between PSMA-PET/CT-PERCIST response and biochemical response criteria（P > 0.05）.Mean SUVmax of the post-treatment prostate cancer was 6.7 ± 2.88.There were 3 pathological complete responders,11 partial pathologic responders and 3 nonpathological responders.The difference of post-treatment tumor SUVmax among the pathological response status was statistically significant（0-1 pathological complete response 3.60,IQR 3.50-4.00,2 partial pathological response 6.15,IQR 4.40-10.70 vs.3 nonpathological response 14.20,IQR 12.50-15.30,P < 0.01）.A significant correlation was revealed between the SUVmax value of the post-treatment primary tumors and the pathologic response by Spearman correlation test（r = 0.849,P > 0.01）.Conclusions:PSMA PET/CT is a promising imaging modality for assessing response to systemic therapy in metastatic hormone-sensitive prostate cancer.PSMA-PET/CTPERCIST can help predict tumor responses.SUVmax of the post-treatment primary tumor may serve as a predictive biomarker for pathological response. |
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